In the last few years, the importance of regulatory small RNAs (sRNAs) as mediators of a number of cellular processes in bacteria has begun to be recognized. Although instances of naturally occurring antisense RNAs have been known for many years, the participation of sRNAs in protein tagging for degradation, modulation of RNA polymerase activity, and stimulation of translation are relatively recent discoveries (see Wassarman, K. M. et al. 1999 Trends Microbiol 7:37–45 for review; Wassarman, K. M. and Storz, G. 2000 Cell 101:613–623). These findings have raised questions about how extensively sRNAs are used, what other cellular activities might be regulated by sRNAs, and what other mechanisms of action exist for sRNAs. In addition, prokaryotic sRNAs appear to target different cellular functions than their eukaryotic counterparts that primarily act during RNA biogenesis. It is unclear whether this difference between prokaryotic and eukaryotic sRNAs is accurate or stems from the incompleteness of current knowledge. Implicit in these questions is the question of how many sRNAs exist in a given organism and whether the current known sRNAs are truly representative of sRNA function in general.
To date, most known bacterial sRNAs have been identified fortuitously by the direct detection of highly abundant sRNAs (4.5S RNA, tmRNA, 6S RNA, RNase P RNA, and Spot42 RNA), by the observation of an sRNA during studies on proteins (OxyS RNA, Crp Tic RNA, CsrB RNA, and GcvB RNA) or by the discovery of activities associated with overexpression of genomic fragments (MicF RNA, DicF RNA, DsrA RNA, and RprA RNA) (Okamoto, K. and Freundlich, M. 1986 PNAS USA 83:5000–5004; Bhasin, R. S. 1989 Studies on the mechanism of the autoregulation of the crp operon of E. coli K12 In: Dept. of Biochemistry and Cell Biology, State University of New York at Stonybrook; Urbanowski, M. L. et al. 2000 Mol Microbiol 37:856–868; Wassarman, K. M. and Storz, G. 2000 Cell 101:613–623; Majdalani, N. et al. 2001 Mol Microbiol 39:1382–1394; for review see Wassarman, K. M. et al. 1999 Trends Microbiol 7:37–45). None of the E. coli sRNAs were found as a result of mutational screens. This observation may reflect the small target size of genes encoding sRNAs compared to protein genes, or may be a consequence of the regulatory rather than essential nature of many sRNA functions. The complete genome sequence of an organism provides a rapid inventory of most encoded proteins, tRNAs, and rRNAs, but it has not led to the immediate recognition of other genes that are not translated. In particular, new bacterial sRNA genes have been overlooked, as there are no identifiable classes of sRNAs that can be found based solely on sequence determinants.